Those compounds that simulate estrogen-like actions have extensive applications for treatment and prophylaxis, including alleviating menopausal symptoms, curing acnes, treating dysmenorrheal and dysfunctional uterine bleeding, osteoporosis and prostate cancer, and preventing cardiovascular diseases.
As found by investigation, estrogen receptors are classified into two types, i.e. ERα and ERβ. Upon binding with these two subtypes, ligands exert physiological actions with different tissue specificities.
A compound that can results in a positive reaction but has no adverse side effect or reduced side effects, like an estrogen replacement therapy, is needed in the field. It is also required that this compound has an estrogen-like action on organisms with a tissue specificity. Due to their spatial structure similarity with estrogen, furochromene derivatives can simulate estrogen, bind to estrogen receptors in organisms, and thus exert physiological actions.
The compound of the invention is a ligand for an estrogen receptor. The compound can be used in treating and preventing various diseases related with the function of estrogen, including bone loss, bone fracture, osteoporosis, metastatic bone diseases, periodontal diseases, cartilage degeneration, endometriosis, uterine fibroma diseases, hot flushes, elevated LDL cholesterol level, cardiovascular diseases, cognitive function impairment, cerebrum degeneration diseases, anxiety, depression caused by insufficient estrogen, inflammation, inflammatory bowel diseases, sexual dysfunction, hypertension, retinal degeneration and cancers, particularly breast cancer, ovary cancer, osteosarcoma, endometrial carcinoma and prostate cancer.
Estrogen is a class of important hormonal compounds in human bodies. When women go into menopause, their estrogen level will drop, thereby causing climacteric syndrome, osteoporosis, senile dementia and cardiovascular system diseases etc. Regarding the dropped estrogen level during postmenopausal period, an estrogen replacement therapy (ERT) can be used, so as to significantly reduce the incidence of osteoporotic fracture and coronary heart disease during postmenopausal period (Turner R T, Riggs B L, Spelsberg T C. Endocr Rev, 1994, 15 (3): 275-300; Mora S, Kershner D W, Vigilance C P, et al. Curr Treat Options Cardiovasc Med, 2001, 3 (1): 67-79). However, ERT might induce breast cancer and endometrial carcinoma (Persson I, Weiderpass E, Bergkvist L, et al. Cancer Causes Control, 1999, 10 (4): 253-260). In order to overcome the adverse side effect of estrogen to cause cancers, a hormone replacement therapy (HRT) which involves the joint action of estrogen and progestogen has been further developed. Nevertheless, a long-term HRT might also increase the incidence of breast cancer. In other words, even though progestogen is used, the occurrence of endometrial carcinoma caused by estrogen cannot be avoided in all circumstances. Therefore, these adverse side effects limit the long-term application of HRT. Moreover, selective estrogen receptor modulators (SERMs) exert estrogen-like actions on bone and cardiovascular systems, and exhibit anti-estrogen function against uteri and breasts. However, utilization of zitazonium and raloxifene can results in some adverse side effects such as endometrial carcinoma and hot flashes, etc. (Fisher B, Costantino J P, Wickerham D L, et al. J Nati Cancer Inst, 1998, 90:1371-1388; Walsh B W, Kuller L H, Wild R A, et al. J Am Med Assoc, 1998, 279:1445-1451).